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Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma
http://hdl.handle.net/10069/0002000365
http://hdl.handle.net/10069/0002000365e507e696-2c0b-4f4f-a2aa-9fec9672e1c1
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ISYK1545_Umeyama.pdf (2 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2023-11-09 | |||||||
| タイトル | ||||||||
| タイトル | Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | γδ T cell | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | malignant pleural mesothelioma | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | natural killer receptor | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | nitrogen-containing bisphosphonate prodrug | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | phosphoantigen | |||||||
| キーワード | ||||||||
| 言語 | en | |||||||
| 主題Scheme | Other | |||||||
| 主題 | immunotherapy | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 |
梅山, 泰裕
× 梅山, 泰裕
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| 著者別名 | ||||||||
| 姓名 | Umeyama, Yasuhiro | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Introduction: Malignant pleural mesothelioma (MPM) is a rare and highly aggressive thoracic tumor with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors exhibit a promising effect in some patients with unresectable MPM in clinical trials, the majority of MPM patients show only modest response rates to the currently available treatments. It is thus imperative to develop novel and innovative therapeutic modalities for MPM, including immune effector cell-based therapies. Methods: γδ T cells were expanded using tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2, and the therapeutic potential of γδ T cells was examined through analyzing cell surface markers and cellular cytotoxicity against MPM in vitro using a europium chelate-based time-resolved fluorescence assay system and a luciferase-based luminescence assay system. Results and discussion: We successfully expanded γδ T cells from peripheral blood mononuclear cells of healthy donors and MPM patients. γδ T cells expressed natural killer receptors such as NKG2D and DNAM-1 and exhibited a moderate level of cytotoxicity to MPM cells in the absence of antigens. The inclusion of PTA, (E)-4-hydroxy-3- methylbut-2-enyl diphosphate (HMBPP) or zoledronic acid (ZOL) induced a TCR-dependent cytotoxicity in γδ T cells and secreted interferon-γ (IFN-γ). In addition, γδ T cells expressing CD16 exhibited a significant level of cytotoxicity against MPM cells in the presence of an anti-epidermal growth factor receptor (EGFR) mAb, at lower concentrations than in clinical settings, whereas a detectable level of IFN-γ was not produced. Taken together, γδ T cells showed cytotoxic activity against MPM in three distinct mechanisms through NK receptors, TCRs and CD16. Since major histocompatibility complex (MHC) molecules are not involved in the recognition, both autologous and allogeneic γδ T cells could be used for the development of γδ T cell-based adoptive immunotherapy for MPM. | |||||||
| 言語 | en | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第1545号 学位授与年月日:令和5年9月6日 | |||||||
| 言語 | ja | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Author: Yasuhiro Umeyama, Hirokazu Taniguchi, Hiroshi Gyotoku, Hiroaki Senju, Hiromi Tomono, Shinnosuke Takemoto, Hiroyuki Yamaguchi, Mohammed S. O. Tagod, Masashi Iwasaki, Yoshimasa Tanaka and Hiroshi Mukae | |||||||
| 言語 | en | |||||||
| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Citation: Frontiers in Immunology, 14, art. no. 1058838; 2023 | |||||||
| 言語 | en | |||||||
| 書誌情報 |
en : Frontiers in Immunology 巻 14, p. art. no. 1058838, 発行日 2023-09-06 |
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| ISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1664-3224 | |||||||
| DOI | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.3389/fimmu.2023.1058838 | |||||||
| 権利 | ||||||||
| 言語 | en | |||||||
| 権利情報 | © 2023 Umeyama, Taniguchi, Gyotoku, Senju, Tomono, Takemoto, Yamaguchi, Tagod, Iwasaki, Tanaka and Mukae. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | 悪性胸膜中皮腫に対するヒトγδT細胞による細胞毒性の３つの異なるメカニズム | |||||||
| 言語 | ja | |||||||
| 出版者 | ||||||||
| 出版者 | Frontiers Media S.A. | |||||||
| 言語 | en | |||||||
| 関係URI | ||||||||
| 識別子タイプ | HDL | |||||||
| 関連識別子 | http://hdl.handle.net/10069/0002000216 | |||||||
| 学位名 | ||||||||
| 言語 | ja | |||||||
| 学位名 | 博士(医学) | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 17301 | |||||||
| 学位授与機関名 | Nagasaki University (長崎大学) | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2023-09-06 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲医歯薬第1545号 | |||||||
| 学位の種類 | ||||||||
| 言語 | ja | |||||||
| 値 | 課程博士 | |||||||
| 引用 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | Nagasaki University (長崎大学), 博士(医学) (2023-09-06) | |||||||
